Dietary cholesterol increases ventricular volume and narrows cerebrovascular diameter in a rabbit model of Alzheimer’s disease

Abstract

Using structural magnetic resonance imaging in a clinical scanner at 3.0 Tesla, we describe results showing that following twelve weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit – effects that are also seen in patients with Alzheimer’s Disease.

Intrinsic connectivity of neural networks in the awake rabbit

“…Many of the same networks found in humans, non-human primates, and rodents are also found in the rabbit. Our findings provide the first examination of the rabbit as a potential animal model for translational research studying neural networks and provide the baseline data for changes that may occur during different behavioral states or disease states such as Alzheimer's disease (Deci et al, 2012; Liu et al, 2012; Perez-Garmendia et al, 2014; Schreurs et al, 2013). …”

Cholesterol and Copper Affect Learning and Memory in the Rabbit

“…The four panels of Figure 4 show structural MRI scans of rabbits that received normal chow and distilled water (a), normal chow and 0.12 ppm copper added to the distilled water (b), 2% cholesterol and distilled water (c), and 2% cholesterol and copper (d), with insets that show the area of the third ventricle. The data in Figure 4 illustrate clearly that a cholesterol diet significantly increased the area of the third ventricle and consequently, when the entire rabbit brain was analyzed, the volume of the third ventricle was found to be higher for the cholesterol-fed rabbits than the normal chow-fed controls [72]. This was true regardless of whether the rabbits were given copper in the drinking water or whether the concentration of that copper was 0.12 ppm [72] or 0.24 ppm [61].…”

“…The data in Figure 4 illustrate clearly that a cholesterol diet significantly increased the area of the third ventricle and consequently, when the entire rabbit brain was analyzed, the volume of the third ventricle was found to be higher for the cholesterol-fed rabbits than the normal chow-fed controls [72]. This was true regardless of whether the rabbits were given copper in the drinking water or whether the concentration of that copper was 0.12 ppm [72] or 0.24 ppm [61]. In all of these experiments, the levels of beta amyloid immunoreactivity to the 10D5 antibody was always higher in cholesterol-fed rabbits than normal chow controls, and the addition of copper tended to increase the intensity of that immunoreactivity even further although this copper-induced increase was not always significantly higher [48–50, 61].…”

“… Figure 5 shows the blood vessels in a rabbit brain that were visualized by time-of-flight angiography during our MRI studies and they include the common carotid arteries, the basilar artery, the internal carotids, and the posterior communicating arteries [67]. Figure 6 shows that the basilar, internal carotid, and posterior communicating arteries were all narrowed by a 2% cholesterol diet compared to normal chow controls and that the addition of 0.12 ppm copper to the drinking water did not significantly increase the narrowing [72]. There were no significant differences in diameter of the common carotid arteries.…”

“…The data show significant increases in the area of the third ventricle as a function of being fed cholesterol. Data are modified from [72]. …”